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Biomedical subjects

A Lau

Publications and source records attributed to A Lau.

At least 73 records · Page 4Linked to original sources
PubMed1992

A randomized, double-blind, placebo-controlled trial to evaluate the effect of enalapril in patients with clinical diabetic nephropathy.

It is unknown if the antiproteinuric effect of angiotensin-converting enzyme (ACE) inhibitors reflects attenuation in the rate of progression of diabetic nephropathy. We report the results of a randomized, double-blind clinical trial designed to evaluate the longitudinal (18-month) effect of the ACE inhibitor, enalapril (5 to 40 mg/d), versus a placebo on 24-hour urinary protein excretion and on the rate of progression of renal disease in 33 patients with clinical diabetic nephropathy. Systemic blood pressure was controlled throughout the trial with conventional antihypertensive drugs. Glomerular filtration rate (GFR), determined by Tc99mDTPA renal clearance, and urinary protein excretion were monitored at 3-month intervals. Enalapril, in contrast to placebo therapy, was associated with an initial (40%) and sustained (33%) decrease in urinary protein excretion. Patients randomized to both enalapril or placebo experienced mean decreases in GFR, from 1.01 mL/s/1.73 m2 (61 mL/min/1.73 m2) to 0.85 mL/s/1.73 m2 (51 mL/min/1.73 m2), and from 1.06 mL/s/1.73 m2 (64 mL/min/1.73 m2) to 0.97 mL/s/1.73 m2 (58 mL/min/1.73 m2), respectively. Eleven of 18 patients (61%) randomized to enalapril, and 10 of 15 (66%) patients randomized to placebo, had a decrease in GFR; their rates of progression were -1.18 mL/min/1.73 m2/mo and -1.00 mL/min/1.73 m2/mo, respectively. In the absence of changes in blood pressure, the addition of an ACE inhibitor to patients with clinical diabetic nephropathy could not be shown to confer a unique renal protective effect. A prolonged decrease in 24-hour protein excretion could not be shown to predict attenuation in the progression of established clinical diabetic nephropathy.

Adult↗
PubMed1992

Central role of tumour necrosis factor, GM-CSF, and interleukin 1 in the pathogenesis of juvenile chronic myelogenous leukaemia.

In previous studies on patients with juvenile chronic myelogenous leukaemia (JCML), we found excessive proliferation of malignant monocyte-macrophage elements in the absence of exogenous growth factor, and impaired growth of normal haematopoietic progenitors. In the current study, six newly-diagnosed JCML patients were investigated to characterize the disease further. In co-cultures, JCML cell culture supernatant as well as patient plasma obtained at diagnosis produced a striking reduction in numbers of control marrow BFU-E, CFU-GM, CFU-Meg and CFU-GEMM colonies. Monoclonal anti-tumour necrosis factor alpha neutralizing antibodies (anti-TNF-alpha Ab) abolished these inhibitory properties. In sharp contrast, JCML supernatants exerted a marked growth-promoting effect on autologous JCML cells cultured in clonogenic assays. Anti-TNF-alpha Ab and anti-granulocyte-macrophage colony-stimulating factor neutralizing antibodies (anti-GM-CSF Ab) both reversed the stimulating effect. Recombinant GM-CSF and recombinant TNF alpha produced a profound increase in JCML colonies when tested individually and anti-GM-CSF Ab reversed the TNF-alpha effect. Expression studies of TNF-alpha and TNF-alpha receptor genes of cultured JCML cells demonstrated mRNAs for both. Further, TNF-alpha activity was assayed in a wide variety of cell culture supernatants and in normal and patients' plasma, and only the JCML specimens showed increased TNF-alpha values. Recombinant interleukin-1 alpha (IL-1 alpha) also stimulated JCML colony growth, but polyclonal anti-IL-1 neutralizing antibodies did not suppress JCML colony numbers nor did it reverse the effects of TNF-alpha or GM-CSF. The evidence indicated that the JCML monokine which inhibits normal haematopoiesis is TNF-alpha and that the endogenously-produced TNF-alpha and GM-CSF from JCML cells play an important role in the pathogenesis of the disease by acting as autocrine growth factors. IL-1 alpha also stimulates JCML cell proliferation as an accessory factor and augments the effect of GM-CSF, TNF-alpha or both.

Base Sequence↗
PubMed1992

Connectedness versus separateness: applicability of family therapy to Japanese families.

This article, a product of the two authors' multicultural experiences, contrasts British and Japanese families in order to examine the applicability of the Western model of family therapy to Japanese families and therapists. Areas where the Western model is incompatible are identified, and modifications to fit the Japanese indigenous model are suggested. The most significant difference in value systems between the two cultures is the Japanese preference for connectedness. The Japanese person is seen as a part of the embedded interconnectedness of relationships, whereas British norms prioritize separateness and clear boundaries in relationships, individuality, and autonomy. This value orientation is manifested in the Japanese language, hierarchical nature of the family structure, the family life cycle, and the implicit communication style. Systemic thinking, which deals with the pattern of relationships, is valid for all families regardless of cultural differences. But therapists should note that the preferred direction of change for Japanese families in therapy, is toward a process of integration--how a person can be effectively integrated into the given system--rather than a process of differentiation. An authoritative therapist style, the use of individual sessions, silence, and other nonverbal techniques are relevant to bringing about the desired change toward better integration of the individual with his or her networks.

Adolescent↗
PubMed1991

The effect of nifedipine GITS on renal function in hypertensive patients with renal insufficiency.

Twelve hypertensive patients with moderately severe renal dysfunction were entered into a protocol to assess the blood pressure and renal effects of the sustained release calcium antagonist, nifedipine GITS (30-180 mg/d given once a day) administered for 5 weeks. Nifedipine GITS monotherapy effectively lowered blood pressure in 50% of the patients. Glomerular filtration rate and effective renal plasma flow were increased 18% and 20%, respectively. The filtration fraction and urinary protein excretion remained unchanged. Changes that were observed in renal function were independent of the blood pressure responses of the patients; there was no correlation between the systemic and renal effect of nifedipine GITS monotherapy. Patients who had a poor systemic blood pressure response exhibited an increase in glomerular filtration rate (+11%) but had a decrease in effective renal plasma flow (-6%); patients who achieved a goal blood pressure response showed increases in both glomerular filtration rate (+35%) and effective renal plasma flow (+40%). These results show that nifedipine GITS monotherapy has the potential to improve renal function abnormalities that are encountered in hypertensive patients with renal disease; the improvement in renal function may be independent of their effect on systemic blood pressure.

Blood Pressure↗
PubMed1991

Women's perspectives on chronic illness: ethnicity, ideology and restructuring of life.

This inquiry into the lives of women living with a chronic illness brings to attention the complex processes that frame the existential meanings of illness. Data from immigrant Chinese and Anglo-Canadian women with diabetes are used to show that illness is constructed in a complex social, political and economic nexus. When the circumstances of women's lives are examined, styles of managing illness that could be attributed to ethnicity, become recognizable as pragmatic ways of dealing with the harsh realities of material existence. It is argued that the trends toward individualizing social problems, and shifting the responsibility for caretaking from the state to the individual, obfuscate the social context of illness, and exclude the socially disadvantaged from adequate health care.

Adaptation, Psychological↗
PubMed1990

The protean manifestations of hemorrhagic fever with renal syndrome. A retrospective review of 26 cases from Korea.

Twenty-six cases of hemorrhagic fever with renal syndrome from 1981 to 1986 were retrospectively reviewed to determine the scope of clinical presentation and the unique complications of the illness. The diagnosis was confirmed by detection of Hantaan virus antibody in 25 cases and by characteristic autopsy findings in 1 case. The illness could be classified into three distinct clinical subgroups. Fever was universally present. Two patients presented with intractable shock and diffuse hemorrhage and died within 6 days from multi-organ system failure, mimicking the clinical picture of overwhelming sepsis. Eighteen patients presented with acute renal failure with an illness lasting a mean of 21 days (range, 10 to 36 days). Resolution of thrombocytopenia heralded recovery of renal function. At discharge, the serum creatinine level was normal in 13 patients; 5 patients had evidence of minimal renal dysfunction. Acute pulmonary edema requiring hemodialysis and retroperitoneal hemorrhage were the major complications in this subgroup. Six patients had an undifferentiated febrile illness with normal renal function. Fever, thrombocytopenia, abnormal urinalysis, hypertransaminasemia, and a benign clinical course characterized the third clinical pattern. The recent availability of serodiagnostic methods to detect Hantavirus group antibody facilitates the diagnosis of hemorrhagic fever with renal syndrome. Application of this test in the described clinical settings will identify unsuspected cases, broaden the knowledge of the geographic distribution of Hantavirus infection, and increase physician awareness of its protean manifestations.

Acute Kidney Injury↗
PubMed1990

Clinical course and pharmacokinetics following a massive overdose of amphotericin B in a neonate.

Amphotericin is the drug of choice for the treatment of fungal infections in infants and children. When used in the recommended doses, amphotericin therapy is associated with high rates of adverse effects, including nephrotoxicity, hepatotoxicity, decrease in white blood cells, platelets and hemoglobin, chills, fever and even death (1). We report a case involving a neonate who was exposed to a 50 fold overdose of Amphotericin over a three day period.

Amphotericin B↗
PubMed1990

Psychological problems in adolescents from ethnic minorities.

This article reviews clinical and theoretical issues of particular importance in working with adolescents of black and white minority origin. This includes differences in definition of competence and stage-specific family tasks through the life cycle. A checklist covering basic points in an ethnocultural sensitive assessment is presented. It is argued that in order to be effective, therapeutic strategies need to mobilize strengths within an ethnocultural context.

Adolescent↗
PubMed1989

Effect of benazepril monotherapy in subjects with hypertension associated with renal dysfunction.

Nine hypertensive patients with mild to moderate renal dysfunction were entered into a protocol to assess the blood pressure, humoral and renal effects of the angiotensin converting enzyme inhibitor, Benazepril (CGS14824A, 2 to 20 mg twice daily) in patients with hypertension and moderate renal insufficiency (mean creatinine clearance 56 ml/min/1.73 m2). Specifically monitored, prior to and following 12 weeks of Benazepril monotherapy, were plasma renin activity and plasma aldosterone, the clearances of creatinine, Tc99m-diethylenetriaminepentaacetic acid (TC99m-DTPA) and para-amino-hippurate, and the 24-hour urinary excretion of protein. Blood pressure was well controlled. Plasma renin activity was stimulated, and plasma aldosterone was suppressed. Mean serum potassium increased from 3.9 to 4.2 mEq/L. Benazepril monotherapy had no adverse renal hemodynamic effect. Benazepril appears to be an effective antihypertensive agent in hypertensive patients with moderately impaired renal function.

Aged↗
PubMed1989

Short-term and long-term renal response to nifedipine monotherapy.

Twenty-six essential hypertensive patients were entered into a protocol to assess the blood pressure and renal effects of the dihydropyridine calcium antagonist, nifedipine (30 to 120 mg/d given in divided dosage) administered for twelve weeks. Nifedipine monotherapy effectively lowered blood pressure. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were increased following short-term therapy (four weeks); however, there was no net change in GFR or ERPF (compared to placebo) following long-term therapy (12 weeks). Renal vascular resistance was reduced. The filtration fraction and urinary albumin excretion was unchanged throughout the 12-week protocol. We conclude that nifedipine monotherapy does not adversely effect renal function. Tolerance occurs to the initial renal vasodilator response; hyperfiltration and hyperperfusion do not persist.

Clinical Trials as Topic↗
PubMed1988

Interferon and phorbol esters down-regulate sIgM expression by independent pathways.

We studied the effects of recombinant interferon, 12-0-tetradecanoylphorbol-13-acetate (TPA), and phorbol 12, 13 dibutyrate (PDB) on surface immunoglobulin expression by Daudi cells. Incubation of cells with recombinant alpha 2 interferon (IFN-alpha 2) caused a 2.5-fold (60%) decrease in sIgM expression as measured by relative fluorescence index (RFI) using a flow cytometer. This decrease in sIgM expression was independent of inhibitory effects on proliferation and cell cycle progression. TPA or PDB also caused a threefold (67%) decrease in sIgM expression, while enhancing proliferation and cell cycle progression. Coincubation of cells with IFN-alpha 2 and TPA decreased sIgM expression by more than fourfold (greater than 75%), which was greater than the decrease induced by the optimal concentration of either agent alone. Molecular studies demonstrated that the treatment of cells with IFN-alpha 2 or TPA decreased the steady-state levels of mRNA for the heavy chain of IgM (c mu), suggesting that down-regulation of sIgM occurred at a pretranslational level. Activation of the cell membrane sodium/proton antiport did not play an integral role in the IFN-alpha 2 or phorbol-ester-induced pathway of sIgM down-regulation. Whereas IFN-alpha 2 induced an increase in the activity of 2',5'-oligoadenylate (2-5A) synthetase, the addition of TPA to IFN-alpha 2 caused a significant decrease in the activity of this enzyme. Although IFN-alpha 2 and TPA exhibited additive effects on sIgM expression, they had opposing effects on cell proliferation, cell cycle progression, and induction of 2-5A synthetase activity, suggesting that these agents down-regulate sIgM expression through independent pathways.

2',5'-Oligoadenylate Synthetase↗
PubMed1988

Pharmacokinetics and adverse effects of amphotericin B in infants and children.

The pharmacokinetics and safety of amphotericin B infusion were studied in 13 infants and children (age range 3 weeks to 18 years; median age 11 years) treated with the drug for proved (n = 11) or suspected (n = 2) fungal infections. The dose during the first day was 0.5 mg/kg, followed by a daily dose of 1 mg/kg for the rest of the treatment period in most patients. The drug was infused over 4 to 6 hours. During the first day, serum concentrations were above the target therapeutic level of 0.3 microgram/ml in all patients at 2 and 6 hours from the start of the infusion, in 12 of 13 patients at 12 hours, but in only 6 of 13 patients at 24 hours. On the third day, all concentrations were greater than 0.3 microgram/ml throughout the 24-hour period, and in 12 of 13 patients were greater than 0.5 microgram/ml. The same kinetic profile prevailed on days 7 to 10 of therapy, with a tendency for increasing concentrations. Elimination half-life was 9.93 +/- 1.5 hours (mean +/- SEM), clearance rate 26 +/- 5 ml/kg.hr, and distribution volume 378 +/- 25 ml/kg. The half-life inversely correlated with patient's age. Pharmacokinetic values calculated during the first day were not different from those calculated on day 3. Significant decreases in hemoglobin, platelets, and serum potassium concentration were recorded along with significant increases in serum creatinine, urea, and aspartate transaminase values. Because of the large pharmacokinetic variability and the high rate of serious adverse effects, individualized dosing of amphotericin B based on therapeutic drug monitoring should be considered.

Adolescent↗
PubMed1988

Effect of nifedipine on renal function in patients with essential hypertension.

Twenty-six essential hypertensive patients were entered into a protocol to assess the blood pressure and renal effects of the dihydropyridine calcium antagonist nifedipine (30-120 mg/day given in divided doses) administered for 4 weeks. Nifedipine monotherapy effectively lowered blood pressure in 73% of the patients. Glomerular filtration rate and effective renal plasma flow were increased 13.3 and 19.6%, respectively. The filtration fraction and urinary albumin excretion remained unchanged. Renal vascular resistance was markedly reduced (25.2%). Changes observed in renal function were independent of the patients' initial glomerular filtration rate. Furthermore, there was no correlation between the systemic and renal effects of nifedipine monotherapy. Patients with a poor systemic blood pressure response exhibited increases in both glomerular filtration rate (+13%) and effective renal plasma flow (+20%), changes comparable with increases in glomerular filtration rate (+13%) and effective renal plasma flow (+19%) observed in patients achieving a goal blood pressure response (diastolic blood pressure less than or equal to 90 mm Hg, or a greater than or equal to 10 mm Hg decrease in diastolic blood pressure, or both). These results suggest that nifedipine monotherapy has the potential to improve renal function abnormalities encountered in the essential hypertensive state independently of its effect on systemic blood pressure.

Adult↗
PubMed1987

Efficacy, electrocardiographic and renal effects of intravenous diltiazem for essential hypertension.

The acute systemic blood pressure, electrocardiographic and renal function responses to an intravenous bolus infusion of diltiazem (0.2 to 0.5 mg/kg) were evaluated in 18 subjects with mild to moderate essential hypertension. Although a significant blood pressure response occurred within 5 minutes, blood pressure returned to pretreatment levels within 1 to 3 hours. After drug infusion, a variety of rhythm and conduction disturbances were noted; the most important were transient prolongation of the PR Interval (first-degree atrioventricular block), a single episode of second-degree atrioventricular block (Mobitz I) associated with T-wave inversion and a transient episode of junctional escape rhythm and atrioventricular dissociation. Intravenous diltiazem had no consistent effect on glomerular filtration rate or effective renal plasma flow. Natriuresis and kaliuresis were observed only at the highest infusion dose. It is concluded that an alternative dosing regimen will be required if intravenous diltiazem is to be used safely and effectively to control blood pressure in patients with hypertensive disease.

Blood Pressure↗
PubMed1987

The acute and chronic effects of betaxolol on blood pressure, renin-aldosterone, and renal function in essential hypertension.

The effects of betaxolol, a long-acting, lipid-soluble, cardioselective, beta-adrenergic antagonist on renal function have not been previously reported. The present study was designed to prospectively assess the acute and chronic antihypertensive, humoral, and renal response to betaxolol, administered once daily, to patients with essential hypertension. After a four-week placebo run-in period, 13 patients with essential hypertension were treated with betaxolol monotherapy for a total of eight months. Results indicate that blood pressure is reduced, and renal function remains stable. These findings are consistent with previous observations with other beta-adrenergic antagonists.

Adrenergic beta-Antagonists↗
PubMed1987

A comparison of betaxolol and nadolol on renal function in essential hypertension.

Betaxolol, a beta 1-selective adrenergic antagonist, and nadolol, a nonselective beta-adrenergic antagonist are both potent long-acting antihypertensive drugs. The effects of betaxolol on renal function have not been reported. The effects of nadolol on renal function are controversial. The current randomized double-blind study was designed to compare the effects of betaxolol and nadolol on glomerular filtration rate, assessed by creatinine and inulin clearances, and renal hemodynamics, assessed by p-aminohippurate clearance. Following a 4-week placebo run-in period, 15 patients with essential hypertension were randomized to a mean dose of 22 mg betaxolol for 12 weeks, and 12 patients with essential hypertension were randomized to a mean dose of 103 mg nadolol for 12 weeks. Results indicate that neither drug produced a clinically relevant effect on renal function. These findings are consistent with previously reported observations with other beta-adrenergic blocking drugs. We conclude that neither of the beta-adrenergic antagonists, betaxolol or nadolol, convey a specific renal pharmacologic advantage; both are equally efficacious and safe in the treatment of mild-to-moderate essential hypertension.

Betaxolol↗
PubMed1987

Amlodipine therapy corrects renal abnormalities encountered in the hypertensive state.

Calcium antagonists may increase glomerular filtration rate and renal plasma flow by antagonizing the intrarenal effects of angiotensin II and/or norepinephrine. We prospectively studied the effects of amlodipine, a once-a-day dihydropyridine calcium channel antagonist, in 19 patients with essential hypertension. Studies were performed after 4 weeks of placebo and 6 weeks of amlodipine therapy, and included the assessment of systolic and diastolic BP, renal clearances of inulin and p-aminohippurate, and determination of body fluid composition. Systolic and diastolic BPs were reduced following 6 weeks of amlodipine monotherapy. In spite of significant decreases in mean arterial pressure, there were increases in inulin clearance (+ 13%), and p-aminohippurate clearance (+ 19%). Filtration fraction was not changed. Renal vascular resistance was decreased (-25%). Total blood volume, extracellular fluid volume, and total body water and body weight were not changed. We conclude that amlodipine therapy has the potential to reverse renal abnormalities encountered in the hypertensive state.

Adult↗